Genetics and Progression of Early-onset Substance Dependence and HIV Risk

早发性物质依赖和艾滋病毒风险的遗传学和进展

• 批准号: 8693248
• 负责人: Christian J Hopfer
• 金额: $ 101.49万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8693248
• 关键词: 14 year old; 18 year old; AIDS/HIV problem; ARHGEF5 gene; Address; Adolescence; Adolescent; Adult; Affect; Alcohol abuse; Alcohol or Other Drugs use; Amphetamines; Architecture; Behavior; Behavioral; Biological; Cessation of life; Characteristics; Cocaine; Cocaine Dependence; Cognition; Collaborations; Communities; Comorbidity; Complex; Conduct Disorder; Consultations; Criminal Justice; DNA; Data; Data Collection; Dependence; Development; Disease; Disinhibition; Dizygotic Twins; Drug Addiction; Enrollment; Environment; Environmental Risk Factor; Event; Exhibits; Family; Genetic; Genotype; Goals; HIV risk; Housing; Imprisonment; Individual; Joints; Life; Link; Longitudinal Studies; Marijuana; Measures; Methamphetamine dependence; Monozygotic Twinning; Monozygotic twins; Morbidity - disease rate; National Institute of Drug Abuse; Neurocognitive; Nicotine; Occupational; Opiate Addiction; Opiates; Parents; Participant; Pharmaceutical Preparations; Problem behavior; Public Health; Recruitment Activity; Reporting; Research; Resources; Risk Behaviors; Risk Factors; Role; Sampling; Severities; Sexual Partners; Siblings; Social Environment; Social support; Staging; Substance Addiction; Substance Use Disorder; Symptoms; Testing; Time; Twin Multiple Birth; Unsafe Sex; Work; Youth; addiction; anti social; base; comparative; critical developmental period; design; early onset; early onset substance use; family genetics; follow-up; genetic analysis; genetic epidemiology; high risk; high risk behavior; high risk sexual behavior; injection drug use; mortality; proband; psychosocial; public health relevance; self help; sex; substance abuse treatment; underage drinking; young adult

DESCRIPTION (provided by applicant): The research proposed in this application aims to understand genetic and environmental factors that promote desistance or continuation of problematic substance use and associated high-risk behaviors that began in adolescence. We propose an ~12-year follow-up (6 years after an initial 6-year follow-up) of an extremely affected adolescent sample as they transition into adulthood; this is a critical developmental period when we expect a portion of these individuals to decrease or desist problematic substance use and associated high-risk behaviors, while others will persist with the most serious, destructive behaviors leading to devastatingly high rates of morbidity and mortality. Our central goal is to understand the genetic and environmental factors that delineate these life trajectories. Results from our longitudinal research demonstrate that adolescent-onset substance users, who primarily exhibited abuse of and dependence on marijuana, nicotine, and alcohol during adolescence, progressed in the severity of their substance use five years later. As young adults, they report dramatically high rates of lifetime cocaine (29.2%), amphetamine (29.2%), and opiate (10.8%) use disorders as well as HIV/AIDS-related risk behaviors such as injection drug use (11%) and risky sexual behaviors. Indeed, when compared with community samples, these individuals report more than twice the number of lifetime sexual partners and a 33% higher rate of unprotected sex. Furthermore, they exhibit alarming rates of adult incarceration (55%) and early death (2.6%). This proposal extends our multiple-PI collaboration focused on the genetic epidemiology of adolescent-onset drug dependence. The three specific aims are to: 1) Identify distinct developmental trajectories of substance use, antisocial, and HIV risk behaviors in probands and siblings from adolescence to adulthood. a) Test initial characteristics of the adolescents, such as sex, severity of early onset substance use disorders (SUDs) and conduct disorder (CD), and neurocognitive functioning (e.g., disinhibition) that predict these trajectories and b) Test whether adult resources such as treatment for SUDs, housing stability, occupational stability, and social support are associated with these trajectories. 2) Determine the genetic and environmental architecture of developmental trajectories of substance use disorders, antisocial and HIV risk behaviors. a) Test the moderating role of social context, such as SES, criminal justice involvement, substance abuse treatment/self-help involvement, and stressful life events, in altering genetic influence and b) Test whether moderating effects vary across developmental periods (adolescence, young adulthood, and adulthood). 3) Test the influence of shared versus specific etiologic influences on measures of SUDs, antisocial behaviors, and HIV risk behaviors across development.

描述（由申请人提供）：本申请中提出的研究旨在了解促进停止或继续有问题的物质使用以及从青春期开始的相关高风险行为的遗传和环境因素。我们建议对受影响严重的青少年样本进行大约 12 年的随访（最初 6 年随访后的 6 年），以帮助他们进入成年期；这是一个关键的发展时期，我们预计这些人中的一部分人会减少或停止有问题的药物使用和相关的高风险行为，而其他人将坚持最严重的破坏性行为，导致极高的发病率和死亡率。我们的中心目标是了解描绘这些生命轨迹的遗传和环境因素。我们的纵向研究结果表明，青少年发作的药物滥用者主要在青春期表现出对大麻、尼古丁和酒精的滥用和依赖，五年后其药物使用的严重程度有所进展。作为年轻人，他们报告终生可卡因（29.2%）、安非他明（29.2%）和阿片类药物（10.8%）使用障碍以及与艾滋病毒/艾滋病相关的危险行为（例如注射吸毒（11%）和危险性行为）的比率非常高。事实上，与社区样本相比，这些人一生中性伴侣的数量是其两倍多，无保护性行为的比例也高出 33%。此外，它们的成人监禁率（55%）和过早死亡率（2.6%）令人震惊。该提案扩展了我们的多 PI 合作，重点关注青少年药物依赖的遗传流行病学。这三个具体目标是： 1) 确定先证者和兄弟姐妹从青春期到成年的物质使用、反社会和艾滋病毒危险行为的独特发展轨迹。 a) 测试青少年的初始特征，例如性别、早发性物质使用障碍 (SUD) 和品行障碍 (CD) 的严重程度，以及预测这些轨迹的神经认知功能（例如去抑制） b) 测试成人资源（例如 SUD 治疗、住房稳定性、职业稳定性和社会支持）是否与这些轨迹相关。 2) 确定物质使用障碍、反社会和艾滋病毒危险行为的发展轨迹的遗传和环境结构。 a) 测试社会背景（例如社会经济地位、刑事司法参与、药物滥用治疗/自助参与和压力生活事件）在改变遗传影响方面的调节作用；b) 测试调节作用是否因发育时期（青春期、青年期和成年期）而异。 3) 测试共同与特定病因对 SUD、反社会行为和整个发展过程中的 HIV 风险行为测量的影响。